1. Field of the Invention
The present embodiments provided herein relate generally to the fields of molecular biology and cancer therapies.
2. Description of Related Art
As the molecular and genetic mechanisms of oncogenesis become better elucidated, the focus of cancer therapy has shifted from the tissue to the genetic level (Bishop, 1991). Mutations in two major classes of genes, oncogenes and tumor suppressor genes (TSGs), play central roles in the oncogenic process. TSGs appear to require homozygous deletion or mutation for inactivation, and restoration of TSG expression is feasible in human tumors (Lowe et al., 2004; Roth, 2006). Intratumoral injection of retroviral or adenoviral vectors expressing the wildtype TSG p53 have been performed in patients with locally advanced non-small cell lung cancer and head and neck cancer (Swisher et al., 1999; Roth et al., 1996; Clayman et al., 1998). These studies have demonstrated that viral vectors expressing the TSG p53 can be safely injected into tumors repetitively and can mediate tumor regression. However, because of the systemic immune response, current viral vectors are limited to intratumoral administration, which does not have an effect on tumor metastases, the primary cause of cancer-related death. Thus development of therapies for intravenous, systemic TSG replacement would represent a significant advance.
Homozygous deletions in the 3p21.3 region in lung cancer cell lines and primary lung tumors have lead to the identification of multiple genes with tumor suppressor activity from this region (Lerman et al., 2000).